The major objective of this proposal is to investigate the mechanisms involved in the chronic effects of alcohol on the gastric mucosa, particularly as related to membrane structure, active membrane transport, role of cyclic nucleotides, histamine, prostaglandin and metabolism. Protection against the alterations produced by alcohol will also be investigated. To accomplish these objectives, a number of techniques have been developed and employed: 1) to fully characterize the physiological, biophysical and biochemical properties of the gastric mucosa; 2) to determine the acute effects of ethanol with respect to time sequence and dose response under conditions expected to be physiological; and 3) to determine the effects of ethanol due to chronic administration with careful consideration of the route of administration (many of the conflicting reports in the literature may be attributed to the varied ways in which ethanol is employed in experimental studies). The chronic animal model will incorporate methodology involving the isolated and intact perfused gastric mucosa (many of the preparations listed have been developed and perfected in our laboratories). Measurements include 1) electrophysiological methods (potential difference, shortcircuit current and resistance), 2) unidirectional and net flux studies (Na+, Cl-, K+, and HCO3-), 3) gastric acid secretion, 4) biochemical determinations of carbohydrate intermediates, phospholipid metabolism, non-protein sulfhydryl compounds, ATP, ADP, cyclic AMP, adenyl cyclase, phosphodiesterase, Na+K+ATPase, histamine, prostaglandin and ethanol, and 5) light microscopy, electron microscopy and microprobe.